JPH01149731A - Chronic respiratory disease in birds, poultry cholera and enteritis necroticans - Google Patents

Abstract

PURPOSE: To treat the subject diseases by oral administration of each effective amount of antibiotic LL-E19020α, LL-E19020 β, or salt thereof. CONSTITUTION: Birds infected with Clostridium perfringens, Mycoplasma gallisepticum or Pasteurella multocida are treated by mixing a feed or drinking water with 0.5-1,000 (pref. 1.0-50)ppm of antibiotic LL-E19020 α, LL-E19020β, or a salt thereof afforded by culturing Streptomyces lydicus ssp. tanzanius NRRL18036 in a liquid medium followed by orally administering the birds with the mixture.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to the use of causative agents of gangreous enteritis, chronic respiratory diseases or fowl cholera.
The present invention relates to a method of treating birds infected with A. to reduce and/or eliminate the infection. More specifically, the present invention relates to Clostridium var.
perfringens), Mycoplasma gallisepticum
cum) or Basteulella multocida (Pastu
poultry infected with P. rella multocida, isolated captive birds, pet birds or zoo birds (avi
a pharmaceutically effective amount of antibiotic LL-E], 9020α,
The present invention relates to a method of reducing and/or eliminating these infections by orally administering the antibiotic LL-Ei9020β or a physiologically acceptable salt thereof.

[Description of Preferred Embodiments 1 Although the structures of the antibiotics LL-E 1 9020α and β have not been revealed, they will be explained using their physicochemical properties.

The physicochemical properties of LL-E 1 9020α are as follows.

LL-E19020α 1, approximate elemental analysis C6
2,73, N7.60, N1.0O1028,67 (by difference) 2, Molecular weight 1225 (FABMS) 3, Apparent molecular formula CssHisN O
sr4, Specific optical rotation [α1 min-0 (C0,385, methanol) 5. Ultraviolet absorption spectrum shown in Figure ■ 6. Optical external absorption spectrum KBr disk shown in Figure ■: 3420.
2970.2925.1717.1695.1647.
1617.1525.1445.1365.1092,
I O18cm-'; 7. Proton nuclear magnetic resonance spectrum: Shown in Figure ■ (3
00MHz, CD CQs) 8, Carbon B nuclear magnetic resonance spectrum: Shown in Figure ■ (75
MHz, CDCQ3, ppm downstream from TMS), the significant (signif 1canL) peaks are listed below: 173.3 129.0 97.374.255.
4 17.2171.4 128.6 (2x)
97.0 72.049.8 17.0170.1
128.43 g9.2 71.941.8 (2
x) 14.8145.7 128.38 83
．． 3 69.1 39.8 13.5140.3
128.1 (2x) 81.6 67.5 39.1
10.8137.0 127.5 77.6
66.4 38.8 10.0134.4 127
．． 1 77.0 66.1 32.9133.9
126.3 76.4 63.531.0132.0
120.8 74.6 56.529.9130
．． 1 100.6 74.5 56.023.81
29.5 (2x) 99.0 74.4 55.6
18.12x = 2 overlapping signals LL-E19020β 1, approximate elemental analysis C63,33, N7.72, N
1.16.027.79 (as a difference) 2, molecular weight 12
25 (FABMS)3, apparent molecular formula CssHs
sN O2+4, specific optical rotation [α] Bamboo--17±2(C
0.455, methanol) 5. Ultraviolet absorption spectrum shown in Figure V 6. Infrared absorption spectrum KBr disk shown in Figure ■: 3430.2
970.2930.1712.1648.1620.1
543.1454.1367.1265.1098.1
020.980 cm-'; 7, Proton nuclear magnetic resonance spectrum 2 Shown in Figure ■ (3
00MHz, C, DCQ, ) 8, carbon-13 nuclear magnetic resonance spectrum: Shown in Figure ■ (7
5M HzlCD CQs, ppm downstream of TMS), the significant peaks are: 173.6 99.0 55.4170.
6 98.4 49.6170.0
97.2 41.6 (2x) 145.6
89,2 39.8140.2 83.
3' 39.1136.7 81.6
38.0134.4 77.6 3
2.9133.9 77.5 31.11
32.0 76.2 29.9130.1
75.5 23.7129.1 (2x)
74.6 18.1128.9 7
4.5 17.2128.6 (2x) 74
-2 (2x) 17.0128.5 69,
1 16.2128.4 68.9
13.5128.3 67.5 10
．． 8128.2 66.6 1
0.0127.8 66.1 127.2 64.1 126.5 56.5 120.9 56.0 100.6 55.6 2X = 2 overlapping signals Novel antibacterial agent LL-E l 9020α and LL -E1
9020β is Streptomyces ridicus ssp, Streptomyces Iydicus
s ssp.

tanzan 1us) during cultivation under controlled conditions.

This microorganism was produced by American Cyanamid Company (Amer 1).
can Cyanamid Company's Medical Research Division, Pearl River, N.
Culture number LL-E in Y's culture collection
It is maintained as 19020. A viable culture of this novel microorganism was collected at the U.S. Department of Agriculture's Northern Regional Research Center Patent Culture Collection Research Facility (the Patent Culture Collection Research Facility).
Culture Co11ection Labor
atory, Northern Regional
Research Center, U, S, Depa
rtment of agriculture),
Peoria, Illinois
is) 61604 and is included in the permanent collection. The culture is then NRR for strain indication.
It has been assigned L18036.

Culture L L -E 1902
0 is Manyara, Tanzania, Africa.
) was isolated from a soil sample collected in a meadow near a lake.

Culture LL-E19020 produces short helical spore chains with to-50 spore lengths, occasionally longer chains. These tend to coalesce and form dry black clumps on ISP media such as oatmeal, mineral salt-starch, etc.

The spores have a smooth surface that is revealed by electron microscopy. The strain contains the isomer of diaminopimelic acid and therefore belongs to the genus Streptomyces.

In the ISP test of carbohydrate utilization, LL-E190
20 grows on arabinose, fructose, inositol, mannitol, raffinose, rhamnose, sucrose and xylose.

LL- in the Gordon physiological series where cellulose is not assimilated
E19020 response to Streptomyces ridicus l5P5, to which it is morphologically and physiologically most similar.
The reaction was compared with that of 461.

LL-E19020 differs from 15P5461 in five properties (xanthine hydrolysis, oxalate decarboxylation, acid from erythritol, rhamnose, and β-methyl-D-xyloside) and was therefore named as a subspecies of Streptomyces ridicus.

Table I Regarding the production of these novel antibacterial agents, it should be understood that the invention is not limited to this particular microorganism or to microorganisms fully endowed with the above properties, which are given for illustrative purposes only. .

In fact, this microorganism can be extracted by various means such as X-rays, ultraviolet radiation, N'-methyl-N'-nitro-N'-nitroguanidine, actinophage (actinophage), etc.
It is desired and intended to encompass the use of mutant strains produced from this microorganism by exposure to e.g.

The in vitro antibacterial activity of LL-E19020α and β was determined against Durham-positive and Durham-negative bacterial spectra by the standard agar dilution method.

LL-E l 9020 in 5% sheep blood and 2x reduced concentration
Mueller-Hinton (Muel) containing a or β
ler-Hinton) agar was placed in a Petri dish. 1 to 5 XIO' colonies forming bacterial units on the agar surface were collected using a steals replicator.
ing device). The lowest concentration of antibiotic that inhibited the growth of a bacterial strain after 18 hours of incubation was recorded as the minimum inhibitory concentration for that strain.

The results are shown in Table ■.

The in vivo antibacterial activity of antibiotics LL-EI9020α and β was determined by Charles River Laboratory (Charles R1v).
Female CD-1 from ER Laboratories)
Mice (body weight 20 ± 22) were incubated with 1.7 × 102 CF U/0.5 mj2 of a culture of Streptococcus pyogenes (s, pyogenes) C203 or 6.5 Established by intraperitoneal infection at 0,5 mA. Mice were treated subcutaneously with the indicated doses of test compounds in 0.2% agar in 0.5 mβ 30 minutes before infection. The results of this test are shown in Table ■.

Antibiotics LL-E19020α and LL-E 1902
0β derive their use from their antibacterial activity.

For example, these antibiotics can be used to control bacterial infections as topically applied antibacterial agents and as general disinfectants in the laboratory.

Surprisingly, we found that these antibiotics treat bacterial infections in birds.
ing). In particular, the antibiotics are useful for reducing or eliminating kaiseki enteritis, chronic respiratory disease, and fowl cholera in infected birds.

According to the present invention, successful treatment of infected birds can be achieved using LL-E190.
It has been found that this can generally be achieved by oral administration of 20α, LL-E19020β or a physiologically acceptable salt thereof in or with the feed or drinking water of infected birds. LL-E l 9020α
, LL-E 19020β or a physiologically acceptable salt thereof, usually about 0.5 to 1 OOOppm, preferably 1.0 to 50 ppm, is effective in reducing or eliminating infectious diseases in birds.

In addition, antibiotics LL-E19020α, LL-E1
It has been discovered that a pharmaceutically effective level of 9020β or a physiologically acceptable salt thereof can be administered clostrically to reduce or eliminate the infection.

The above pathogens constantly threaten the poultry industry.
e) is a disease that costs poultry and egg producers many times more than a hundred dollars annually. Causative factors of kaiseki enteritis, chronic respiratory diseases and fowl cholera
agent).

Although the main economic losses from these diseases generally occur in poultry such as chickens, turkeys, geese, and ducks, these diseases can also occur in isolated captive animals such as quail and pheasants, in waterfowl and raptors in zoos, and as companions or pets. It is now well established that this also occurs in exotic and wild birds. It is therefore an object of the present invention to provide a method for treating birds infected with the causative agent of kaiseki enteritis, chronic respiratory disease, or fowl cholera to reduce or eliminate the infection.

General Fermentation Conditions Cultivation of Streptomyces ridicus ssp, Tanzanius NRRL 18036 can be carried out in a wide variety of liquid media. LL-E 19020α and LL-E
l Useful media for the production of 9020β include dextrin,
Assimilable carbon sources such as sucrose, molasses, glycerol; proteins, protein hydrolysates, polypeptides,
Includes assimilable nitrogen sources such as amino acids and corn steep liquor; inorganic anions and cations such as potassium ions, sodium ions, ammonium ions, calcium ions, sulfate ions, carbonate ions, phosphate ions, and chloride ions. Trace elements such as boron, molybdenum, copper, etc. are provided as impurities in other components of the medium. Aeration in tanks and bottles is carried out by forcing sterile air into or onto the surface of the fermentation medium. Stirring in the tank is performed by mechanical stirring blades. Antifoaming agents such as silicone oil can be added if necessary.

LL-E19020 Numerical isolation method for σ and β LL-E
19020α and LL-E19020β were extracted from the culture solution at 4
．． Adjust the pH to 5-5.5, filter through diatomaceous earth, extract into a solvent such as ethyl acetate, concentrate, dissolve in a solvent such as dichloromethane, and continuously use dichloromethane and methanol:dichloromethane (1:4). recovered by purification by silica gel column chromatography,
Give crude product.

The crude product was then separated into α and β components and added to acetonitrile-0.1M ammonium acetate buffer (pH 4.3) (
Further purification by high performance liquid chromatography on a reverse phase column using a 1:l) system.

The invention is further described by the following non-limiting examples.

Example 1 Inoculum (1 noculum) Preparation A typical medium used for initial inoculum growth was prepared according to the following formulation.

Dextrose 1.0% Dextrin 2.0% Yeast extract
0.5%NZ Amine A■1
0.5% calcium carbonate 0.1% Add water (Water &s) 100.0% Note 1
casein pancreatin (pH1create ic
) digestate, 5hefffield Chemica 1 company,
Norwich NY® This medium is adjusted to pH 7.0 and sterilized. Streptomyces ridicus ssp, Tanzanius NRRL18036 in 100+J of this sterile medium in a 500-flask.
mycelial scraps from the agar slopes of
scrapings) was inoculated. The medium was then placed on a rotary shaker and incubated at 28°C for 48 hours.

This first seedling was used to inoculate the same sterile medium 10α in a bottle. A second inoculum was obtained by growing in this medium for 24 hours. 25 of the same sterile medium in the tank with a second inoculum
It was inoculated at 0Q. Use this medium as a mushy substance.
(mash) was grown for 48 hours at 28° C. with a sterile air flow rate of 200 Q per minute, and with stirring by a stirring blade rotated at 22 Orpm.

Example 2 fermentation A fermentation medium with the following formulation was prepared.

Dextrin 3.0% molasses
2.0% soy peptone 0.75% yeast extract 0.25% calcium carbonate
Add 0.2% water 10
This medium was 0.0% sterilized, and then 2700Q was inoculated with the third inoculum 300Q of Example 1. Fermentation is Matshu α
0.5 air per minute! With a sterile air flow rate of 1
28°C under stirring with a stirring blade rotated at 0.00 rpm.
I went there for 113 hours. Then I collected the matshu.

Example 3 Isolation and purification of LL-E19020α and β The recovered matshu of the two fermentations performed as in Example 2 were combined, and the total amount was 600
The solution was brought to 0Q, adjusted to pH 5 with hydrochloric acid, and filtered through diatomaceous earth. The filtrate was extracted with ethyl acetate, and the extract was concentrated to a syrup.

Dissolve this syrup in dichloromethane and place 1000j of silica (60-200 mesh) on a sintered glass funnel.
applied to. The silica column was first eluted with dichloromethane, collecting four 2Q fractions, and then with methanol:dichloromethane (1,:4) to obtain one 4Q fraction. This 40. Both parts were evaporated to dryness, leaving a residue of 120. ? I got it. The residue was redissolved in dichloromethane 4Q and applied to silica 5002 on a sintered glass funnel. This silica was eluted with methanol:dichloromethane (1:4), and one portion was collected. Fractions 1 and 2 were combined and evaporated to give crude LL-E.
19020α and β992 were obtained.

This crude product was dissolved in methanol, reversed phase ram (C1
8 bonded phase (C180onded phase, 40 microns) was applied to 12Q. Column with acetonitrile
〇, IM ammonium acetate buffer (pH 4,3) (1:
1) at a rate of 0, IQ/min. Thirteen 24Q fractions were collected. Fraction 7 is LL
E19020a, fractions 11-13 are LL-E1902
It contained 0β.

Antibiotics were added to the mobile phase using dichloromethane.
LL-E19020alo &
Both L-E19020β142 were obtained as white solids.

Example 4 Bastilleula disk test A sterile paper disk (diameter 〆" (6,35 mm)) was immersed in a 2.5 mg/+nj2 solution of the test compound and
Dry in a 7°C incubator overnight. Prepare standard antibiotic control discs for testing along with test compound discs. 2 until use of dry desif
Store at ~4°C. Two test microorganisms, B. marmesida 31081B and B. haemolytica 30660, were cultured in brain heart infusion medium (brain hemolytica 30660).
art 1nfusion broth) at 37°C
Incubate for 5 hours. A 1:10 dilution of each culture is prepared using Mueller-Vinton broth.

Mueller-Vinton agar 200ml diluted culture solution
-9 inch (22,86 cm) x 9 inch (22,86 cm) manufactured by Nunc
Pour aseptically into a bioassay plate. The use of 9" x 9s plates allows testing of 36 discs per plate. Appropriate discs are applied to the seeded agar plates and incubated at 37°C for 18-20 hours.

Record the zone of inhibition.

T. hyodysenteria
e) Disc test sterile paper disc (diameter 3A# (6,35mm))
was immersed in 2.5 mg/a+β solvent of the test compound, and
Dry in a 7°C incubator overnight. Prepare standard antibiotic control discs for testing along with test compound discs. Until use of drying disc 2
Store at ~4°C. Two T's.

hyo strain B78 (ATCC27164) and B204
(ATCC31212) in brain heart infusion medium (prepared anaerobically) supplemented with 2% fetal bovine serum.
Culture in gaLe culture tubes at 38°C for 24 hours. Culture solution 1a+β was sprinkled on 200 mj2 of trypsinized soybean (trypt 1case) agar containing 5% defibrinated bovine blood, and Nun
Pour aseptically into a bioassay plate (9" x 9#) manufactured by Company C.

The use of 9" x 9# plates allows for the testing of 36 discs per plate. The appropriate discs are applied to the agar plate, followed by 80% nitrogen, 10% carbon dioxide and 10% nitrogen.
Incubate in an anaerobic chamber containing 3800% hydrogen for 24-48 hours until hemolysis is complete. Record the zone of inhibited hemolysis.

Minimum inhibitory concentration by agar dilution method ■ Serial drug I; 2-fold dilutions are prepared in the range of 2560-0.15 meat/mβ using Mueller-Vinton medium. A solvent control is also used.

2. Place drug diluent (IOX) 2- into a sterile screw cap bottle and add Mueller Vinton Agar 18d containing 5.6% defibrinated bare hand blood. Final drug concentration is 5
256-0.015 Itfl in agar containing % sheep blood
/ll1l.

3. Inoculate 2.3 isolated colonies of each test organism into 5-g trypsinized soy broth or brain heart infusion medium. Shake the culture for 5 hours at 35°C.

4 Each culture was grown in Mueller-Vinton medium at 1 = 50 (
10-17) and 5teers replicator (
Apply to the agar plate using a replicator (
appl 1ed). Finally, spray control plates to ensure that viable microorganisms are present during the procedure. The inoculated agar plate is left undisturbed until the inoculum spot is completely absorbed.

5. Invert the plate (1 invert) and incubate for 18 hours at CO2 to 35°C.

6 Minimum inhibitory concentration (MIC) is defined as the lowest concentration of antimicrobial agent at which complete inhibition occurs. Very fine, slightly visible haze or single colonies are ignored.

MIC test microorganism Staphylococcus aureus ArCc 259
23// // 52r Smith Strain” tt tt 14
ATCC6538Ptt //
335 mastitis isolate // tt
335 tt// //
334 tt// //
Penicillin-resistant Streptococcus pyogenes ATCC19615〃〃41 tt // 342tt
u 343 Streptococcus faecalis 42 Dr, Juke'S #80
43 Streptococcus uberis Cornell
Matitis Escherichia coli ATCC25
922〃〃81 // // 80-654 Tetracycline-resistant Basteulella multocida 31081B
(In vitro disc (multocide)
test strain) tt tt 80-35
48 (In vivo mouse model strain) ll// 31451 // // 32301tt
tt 30170B// //
80-5945 Basteulella haemolytica 3
0660 (In vitro disc test strain) tt tt 80-6744tt
tt var, Kunzendo
rf 4 Bordetella pronchiseptica "83 stocks (
Bordetella bronchiseptica
) // // 11
266tt //
31068Bll //
11948A Mycoplasma galliscepticum (M
Minimum Inhibitory Concentration Assay I for Ycop Iasmagallisepticum) Serial 2-fold dilutions of drug stock solutions are prepared in Mycoplasma broth in the range 2560-0.015 μg/ml. A solvent control is also used. These concentrations are 10 times (IOX) the final test concentration.

2 Thaw the frozen (-80°C) stock culture of Mycoplasma gallisepticum “R'' strain, and inoculate the 0.5mβ fraction into Mycoplasma medium 5-.At the same time, 0.1-
is plated on Mycoplasma agar plates to check for purity. Both cultures are grown at 370C. Growth in the medium is indicated by a color change from red to yellow. Growth on agar is observed using a stereoscope.
pe).

3 MIC assays are performed in 96-well microtiter plates. Place 25 μl of IOX drug solution into each test hole. Appropriate solvent controls are also included.

4. Mycoplasma seedlings are prepared by transferring positive cultures to fresh medium at a ratio of 0.2 mj2 culture to 5.0 − medium. If necessary, prepare a large quantity of inoculum using the above formulation.

5. Place 225 volumes of the mycoplasma culture medium inoculated above into each test hole and mix. plastic sealing tape (sea
ler tape) and make a small hole over the center of each test hole with a sterile 25 standard needle. The needle is changed between each drug to avoid cross-contamination of the holes. Additionally, perforate the tape from the lowest concentration of drug to the highest concentration. Final test concentration is 256-0.005μg
/ml, each with a total volume of 250 compositions. Holes containing only seedling medium 250/412 and non-planting medium 2501t1
Add a well containing as an additional control.

6. Incubate the assay plate at 37°C until a color change from red to yellow occurs initially evenly in the test plate. The MIC value is recorded as the concentration at which the broth color (red) remains unchanged.

In these tests, 1 day old
Broiler chicks are placed in a battery chick nursery box (batter).
ybl-ooders) and reared under standard conditions with feed without added drugs until 12 days old. On day 12, the chicks are wing trnded, weighed, and placed in a growing battery (gross) in groups of 10 feathers/pen.
wing batteries). All treatments including infected and uninfected controls were
are replicated.

■Infection control and E19020α and E on the 2nd day 1st
All birds in the treatment groups receiving 5 and 50 ppm of 19020β were infected with Eimeria acervulina.
acervulina) mild challenge (chaf
fenge).

On days 14-18 (5 days in a row), all birds except the uninfected control group are fed with an overnight culture of Clostridium ver. 7 ringens type C.

On day 19, all birds are weighed and three pre-selected birds from each group are killed and necropsied.

The degree of intestinal pathology is as follows.

0 No lesions overall No gross 1esio
ns)l Thin-walled or friable small intestine2 Focal necrosis and/or ulceration3
Large plaques of necrosis 4 Severe, intense necrosis
The remaining birds are held for an additional 7 days, killed, measured, and data recorded.

Measurement data and records Each body weight is measured at 12.19 and 26. feed consumption by 1
Measure on days 2-19 and 26. Intestinal lesion scores are taken on day 19 for 3 birds per group. Each enclosure (pe
Daily health observation for n) will be conducted on days 12-26.

The results obtained are shown below.

Nobori 1. ＼− CO --(Airmouth Mouth p) Country Country Country Examples of research on antibiotics LL for chronic respiratory disease in poultry caused by Mycoplasma gallisepticum
- Performed to evaluate the efficacy of E19020α. Antibiotics 1 from 7 days before challenge to 7 days after challenge
01/ton and 50J/lon in succession. Birds also fed a diet containing chlortetracycline 1009/ton serve as a positive control group. Infected and uninfected, drug-free control groups are also included. Seven days after each treatment diet, the bird's right and left post-thoracic air sacs were
racicair 5acs) are challenged with M and gallisepticum (MG).
ed with). Air sacs from all birds that die after the challenge are cultured for the presence of Mycoplasma. The air sacs of all birds are scored based on gross lesions at death or at necropsy at the end of the study.
ed). Surviving birds at the end of the study will be bled for Mycoplasma gallisebuteicum serology testing prior to necropsy. Measurements of body weight and food intake will be made at study-centered intervals.

From the above data, antibiotic LL-E190 per ton of feed.
20α50I? It can be seen that the Mycoplasma gallisepticum -infected chicks treated had better weight gain, better feed/gain ratio and lower mortality rate than the uninfected chicks.

Features and aspects of the present invention are as follows.

1. Pharmaceutically effective amount of antibiotic LL-E19 for infected birds
A method for treating necrotic enteritis, chronic respiratory disease and fowl cholera in infected birds, comprising orally administering 020α, LL-E19020β or a physiologically acceptable salt thereof.

2. Birds infected with Clostridium verfringens, Mycoplasma gallisepticum or Pasteurella multocida are isolated islands, pet birds, or birds in zoos (avainzoological).
1. The method according to item 1 above, wherein the method is

3. The method according to item 1 above, wherein the antibiotic is orally administered to birds at a concentration of 0.5 to 11,000 pp in or together with the bird feed or drinking water.

4. The method according to item 1 above, wherein the antibiotic is administered to infected chickens or turkeys in feed containing 1.0 to 50 ppm of LL-E19020α, LL-E 1 9020β, or a physiologically acceptable salt thereof.

5. The method according to item 1 above, wherein the antibiotic is administered to infected chickens or turkeys in drinking water containing 1.0 to 50 ppm of LL-E19020α, LL-E19020β, or a physiologically acceptable salt thereof.

6. Antibiotics LL-E19020α, LL-E1902
0β or physiologically acceptable salt thereof 0°5-1000
A method for treating chickens or turkeys infected with kaiseki enteritis, the method comprising orally administering feed or drinking water containing ppm.

7. Antibiotics LL-E19020α, LL-E1902
0β or physiologically acceptable salt thereof 0°5-1000
A method of treating chickens or turkeys infected with chronic respiratory disease, comprising orally administering feed or drinking water containing ppm.

8. Antibiotics LL-E19020α, LL-E1902
0β or a physiologically acceptable salt thereof 0°5~l OOO
A method of treating chickens or turkeys infected with poultry cholera, comprising orally administering feed or drinking water containing ppm.

[Brief explanation of the drawing]

FIG. 1 shows the ultraviolet absorption spectrum of LL-E19020a. FIG. 2 shows the infrared absorption spectrum (KBr disk) of LL-E19020σ. FIG. 3 shows the proton nuclear magnetic resonance spectrum CCDCQ of LL-E19020α (in solution). FIG. 4 shows the carbon-13 nuclear magnetic resonance spectrum (CDCQ, in solution) of LL-E19020a. FIG. 5 shows the ultraviolet absorption spectrum of LL-E19020β. Figure 6 shows the infrared absorption spectrum (KBr disk) of LL-E 19020β. FIG. 7 shows the proton nuclear magnetic resonance spectrum of L L -E 19020β (in CCDCQ3 solution). FIG. 8 shows a carbon-13 nuclear magnetic resonance spectrum (CDCC, in solution). Lunch to Ajiga 9A-￥ Bag

Claims (1)

[Claims] 1. Pharmaceutically effective amount of antibiotic LL-E19 for infected birds
A method for treating gangrenous enteritis, chronic respiratory disease and fowl cholera in infected birds, which comprises orally administering 020α, LL-E19020β or a physiologically acceptable salt thereof. 2. Antibiotics LL-E19020α, LL-E1902
0β or a physiologically acceptable salt thereof 0.5-1000p
1. A method for treating chickens or turkeys infected with gangrenous enteritis, which comprises orally administering feed or drinking water containing PM. 3. Antibiotics LL-E19020α, LL-E1902
0β or a physiologically acceptable salt thereof 0.5-1000p
A method of treating chickens or turkeys infected with chronic respiratory disease, characterized by orally administering feed or drinking water containing PM. 4. Antibiotics LL-E19020α, LL-E1902
0β or a physiologically acceptable salt thereof 0.5-1000p
A method of treating chickens or turkeys infected with poultry cholera, which comprises orally administering feed or drinking water containing PM.